Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet.

Objective: To determine if chronic administration of a low level of dehydroepiandrosterone-sulfate (DHEAS) (10 micrograms/ml drinking water) attenuates adiposity in male Osborne-Mendel rats fed low-fat (11% of kcals) vs high fat (46% of kcals) diets.

Design: Rats were randomly assigned to one of four treatment groups for 6 wk in this 2 x 2 factorial study. The main effects tested were diet (low vs high fat) and DHEAS (- or +).

Subjects: Male Osborne-Mendel rats (initial body wt approximately 265 g).

Measurements: Adipocyte mass, size and number from two major fat depots (retroperitoneal, epididymal); mass of one subcutaneous adipose depot (inguinal); serum levels of triglycerides, insulin, glucose and DHEAS; brown adipose tissue (BAT) mass; body weight gain, food and water consumption, and residual carcass composition.

Results: DHEAS treatment had no effect on weight gain, food consumption or water intake. DHEAS-treated rats fed the high-fat diet had smaller fat pads containing fewer adipocytes and less carcass lipid than the non DHEAS-treated rats fed the high-fat diet. In contrast, DHEAS-treated rats fed the low-fat diet had similar levels of adipose tissue mass and cellularity compared to control animals fed the low-fat diet.

Conclusion: Administration of a low dose of DHEAS (10 micrograms/ml or 0.8 mg/kg body wt/d) in the drinking water of young male Osborne-Mendel rats fed a high-fat diet for 6 wk reduced carcass lipid, fat depot mass and retroperitoneal and epididymal adipocyte number compared to their high-fat-fed cohorts. In this study, the antiobesity effects of DHEAS were specific to the level of dietary fat used.